APCs express DCIR, a novel C-type lectin surface receptor containing an immunoreceptor tyrosine-based inhibitory motif

We have identified a novel member of the calcium-dependent (C-type) lectin family. This molecule, designated DCIR (for dendritic cell (DC) immunorecep tor), is a type II membrane glycoprotein of 237 aa with a single carbohydra te recognition domain (CRD), closest in homology to those of the macrophage lectin and hepatic asialoglycoprotein receptors, The intracellular domain of DCIR contains a consensus immunoreceptor tyrosine-based inhibitory motif , A mouse cDNA, encoding a homologous protein has been identified. Northern blot analysis showed DCIR mRNA to be predominantly transcribed in hematopo ietic tissues. The gene encoding human DCIR was localized to chromosome 12p 13, in a region close to the NK gene complex. Unlike members of this comple x, DCIR displays a typical lectin CRD rather than an NK cell type extracell ular domain, and was expressed on DC, monocytes, macrophages, B lymphocytes , and granulocytes, but not detected on NK and T cells. DCIR was strongly e xpressed by DC derived from blood monocytes cultured with GM-CSF and IL-4, DCIR was mostly expressed by monocyte-related rather than Langerhans cell r elated DC obtained from CD34(+) progenitor cells, Finally, DCIR expression was down-regulated by signals inducing DC maturation such as CD40 ligand, L PS, or TNF-alpha, Thus, DCIR is differentially expressed on DC depending on their origin and stage of maturation/activation. DCIR represents a novel s urface molecule expressed by Ag presenting cells, and of potential importan ce in regulation of DC function.